THE SELECTIVE P2X3R ANTAGONIST DT-0111 DOES NOT AFFECT TASTE IN MICE

Adenosine 5’-triphosphate (ATP) is found in every cell of the human body where it plays a critical role in cellular energetics and metabolism. ATP is released from cells under physiological and pathophysiological conditions. Extracellular ATP acts as an autocrine and paracrine molecule, the effects of which are mediated by cell surface purinergic receptors (P2R). The activation of P2X3R and P2X2/3R localized on vagal sensory nerve terminals has been implicated in the sensation of pain as well as multiple pulmonary disorders including chronic obstructive pulmonary disease (COPD), asthma and chronic cough. DT-0111 is a novel water-soluble molecule that is being developed as a drug candidate for cough suppression and bronchodilation. DT-0111 acts as a selective antagonist at P2X3R vs. P2X2/3R. Because the latter participates in taste sensation, its blockade could explain loss of taste sensation by certain drug candidates targeting P2X3R. Thus, we tested the hypothesis that DT-0111 does not affect taste sensation in a mouse model in vivo. Using the mice-gustometer model, we found that at doses up to x15 the targeted clinical dose (0.142 mg/kg), DT-0111 did not affect taste sensation.